Purpose: Glucose transporters 1 (GLUT1) facilitates glucose uptake in cancer. An inverse relationship between I-131 and F-18 fluorodeoxyglucose (FDG) uptake in PET/CT ("flip-flop phenomenon") was described for thyroid cancers (TCs) during dedifferentiation. We investigated the relationship among GLUT1 expression, proliferation, iodine concentration, and glucose uptake in different TC types, with emphasis on "poorly differentiated thyroid carcinoma" (PDTC).
Methods: For immunohistochemistry, 95 thyroid tumors (follicular adenoma, papillary TC, follicular TC, PDTC, and anaplastic TC [ATC]) were investigated for GLUT1 expression and proliferation (Ki-67 index). For PET/CT study, 47 F-18 FDG PET/CT of patients with TC (22 PDTC), 39 corresponding I-124 PET/CT, and glucose and iodine uptake were evaluated. PTC and FTC were summarized under differentiated TC (DTC).
Results: Immunohistochemistry: 65% of TC expressed GLUT1. The number of GLUT1-positive TC and GLUT1 expression increased with escalating dedifferentiation/aggressiveness of TC types (P < 0.001). A correlation between proliferation and GLUT1 expression was noted (P < 0.001). PET/CT study: F-18 FDG uptake was measured in 81% of cases. Occurrence of F-18 FDG-avid cases as well as median F-18 FDG maximum standardized uptake values were lowest in DTC, intermediate in PDTC, and highest in ATC. Accordingly, numbers of iodine-avid cases and median I-124 maximum standardized uptake value featured an inverse pattern.
Conclusions: Dedifferentiation in TC is accompanied by GLUT1 upregulation and increased proliferation. PDTC was found to be intermediate between DTC and ATC in terms of GLUT1 expression and F-18 FDG or I-124 uptake, suggesting that the flip-flop phenomenon occurs at a dedifferentiation stage in between. Furthermore, the results suggest that F-18 FDG PET/CT is an important imaging modality for ATC and PDTC.